Summary of Study ST001153
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000772. The data can be accessed directly via it's Project DOI: 10.21228/M8WH51 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001153 |
Study Title | Erythrocyte adenosine A2B receptor-mediated AMPK activation: Counteracting CKD by promoting oxygen delivery |
Study Summary | Background: Although the erythrocyte is the most abundant cell type in our body, acting as both a deliverer and sensor of oxygen (O2), its function and regulatory mechanism in chronic kidney disease (CKD) remain unknown. Methods: Unbiased metabolomics screening in the whole blood of mice infused with or without angiotensin II (Ang II) at 140ng/kg/min up to 14 days was conducted. Mice with specific ablation of ADORA2B in erythrocytes and patients with CKD were used to determine its function in CKD, potential mechanisms and human relevance. Results: Unbiased metabolomics revealed that 2,3-biphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite promoting O2 delivery, was significantly induced in an experimental model of CKD induced by Ang II. Mouse genetic studies revealed that erythrocyte ADORA2B signaling via AMPK-stimulated activation of BPG mutase was a key compensatory cellular response to counteract kidney hypoxia, tissue damage and disease progression in Ang II-induced CKD by promoting 2,3-BPG production and O2 delivery. Preclinical studies showed that enhancing AMPK activation offset kidney hypoxia by triggering 2,3-BPG production and O2 delivery. Human translational studies validated mouse findings that erythrocyte 2,3-BPG levels, AMPK activity and O2 delivery capacity were significantly induced in the erythrocytes of CKD patients compared to normal controls and their elevations were correlated to disease severity. Conclusion: Overall, we have provided both mouse and human evidence that ADORA2B-AMPK signaling cascade-induced 2,3-BPG production is a beneficial erythrocyte response to promote O2 delivery to counteract kidney hypoxia and progression of CKD. These findings pave a way to novel therapeutic avenues in CKD. |
Institute | University of Texas Health Science Center at Houston |
Department | McGovern Medical School |
Last Name | Xia |
First Name | Yang |
Address | 6431 Fannin, MSB 6.202,Houston, TX 77030 |
yang.xia@uth.tmc.edu | |
Phone | 713-500-5039 |
Submit Date | 2019-02-18 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | GC-MS |
Release Date | 2019-07-17 |
Release Version | 1 |
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Collection:
Collection ID: | CO001212 |
Collection Summary: | Approximately 1 mL mouse blood was collected with EDTA-contained tube and and stored at −80°C before further analysis. |
Sample Type: | Blood (whole) |